In practical use, they are fairly interchangeable but there is a slight difference in connotation:
Maybe you don't already know that.
This implies that there is a piece of knowledge that you have not previously learned. The implication is that you can learn it now and the speaker can teach it to you. This usage also has an inverted form:
You already know this.
Maybe you don't know it yet.
This implies that you haven't learned something but it is something that can be learned in the future. This usage is also common when someone is making a claim that they are extremely confident about:
Maybe you don't know it yet, but I've already won the championship tomorrow!
"It's idiomatic; you just have to learn it that way" seems to be the canonical answer to these types of questions - but I think that only serves to increase the barrier between native and non-native English-speakers.
These location-themed idioms have a pattern, and they reflect the way I consider the ideas presented with them. They're very visual.
So let's look at 'down to business', as was brought up in a comment. 'Up' and 'down' are relative terms - relative, specifically, to gravity. In the universe of ideas, the gravity of an idea flows toward the core of the primary object. In a meeting, you might have a number of peripheral social layers - greetings, pleasantries, small talk, obscuring the core objective: the 'business'. So, getting down to business means to cut through the peripheral matters and to the core matter at hand. Failing to get 'down to business' would mean resting on the upper layers of the shell, making no effort to penetrate deeper.
To the actual phrase in question, 'what [activity] are you up to?', we have the opposite direction of motion. The concepts in play are the activity and 'you'. Your movement is 'up', away from the gravity of something and moving toward an activity. What is that something? It's your natural state. You're investing energy, against your inertia (the metaphorical gravity of your natural state), to continue some activity. That activity is what you are 'up to'. When the answer is 'nothing', the implication is that the speaker is at rest, and therefore is not 'up'.
Continuing with these common idioms, you could have someone 'putting up a front' versus 'not letting anyone in'. The first implies action - raising a barrier to conceal your natural state. The second implies inaction - exposing only what is naturally visible.
Back to 'up', in addition to being up 'to' some activity, you can also be up 'for' it. In that case, the image is more similar to the energy states of electrons, for example. You still have your rest state at the base, and then you have various potential activities orbiting at varying distances from rest - indicating how far, metaphorically, they are from rest (the level of burden, the amount of stress, the required energy/time/money, or whatever the subject uses to qualify activities). While entirely abstract, the speaker that is up 'for' a certain activity is also necessarily up for all activities that they perceive to be closer to 'rest'. Someone who's feeling 'down' is typically not 'up' for much.
Conversely, you can also be 'down' for some activity. In this case, the activity has gravity, and the speaker has to decide whether to submit to it or not. The important difference is that, because the activity has been given gravity, it's typically less flexible. Someone who's up for drinks might not be down for 'drinks at Bar A on Friday at 7'. Being up for drinks allows you flexibility, while being down for the plan implies submission to that plan.
I hope this helps to clarify the way that some (at least one) native English speakers visualize this type of language - even if they don't realize it. Failing to explain this visual aspect of the English language is, I think, a tragic failure. It's the difference between a logical, beautiful language that eloquently expresses abstract thought and a cumbersome, illogical language full of nonsensical idioms.
Best Answer
The sentence is ambiguous in terms of its meaning because it's ambiguous in terms of its syntax too.
It is possible that the string what you know is a fused relative here (a special kind of relative clause construction sometimes also known as a free relative). In this case the string what you know is a noun phrase. It represents an entity. These kinds of fused relatives with what can be paraphrased using the words the thing(s) that. We can paraphrase the fused relative reading of the sentence (and make it slightly clearer by adding the word same) like this:
In this reading of the sentence we can consider the simple object of the sentence (as opposed to the full grammatical object of the sentence) as the pronoun what. This word represents the actual thing which is unfamiliar, unknown, to the speaker.
Alternatively, the string what you know could be read as an interrogative clause. In this case, if the you concerned was called Bob, for example, the sentence would mean something like:
[I used Bob in the sentence above because the deixis of you could cause further problems here]
Here the whole interrogative clause what you know represents a question, the answer to which is unknown to the speaker.
Grammars like The Cambridge Grammar of the English Language give detailed analyses of the different structures of fused relatives and interrogative clauses. The most pertinent difference is that—according to their analysis—in the fused relative reading what you know is a noun phrase (a phrase headed by a noun or pronoun, in this case the word what) , whereas what you know in the interrogative reading is an interrogative clause (and therefore ultimately headed by a verb, in this case the verb know).
There is a nice test you can do, which will tell you whether an item is a fused relative or an interrogative clause. In the interrogative clause reading you can add the word else after the what and the sentence will still make sense and still be grammatical (although it will have changed its meaning somewhat). So the following sentence can only have the interrogative reading:
The sentence above can only mean: