A phrase used to ask about something odd, or what the point of something is. The word "that" can also be replaced with whatever noun the person is asking about. It is also common to inerject the word "fuck" into the phrase to express shock or discust.
What's up with the smirk?
Look at all those bags on the road. What's up with that?
Person1: What the fuck's up with your hand!?
Person2: Ahh! Why are you just standing there?! Take me to the fucking hospital!
1. A term used by an individual who has not quite made up their mind on a question they have been asked.
2. A response given by an individual who is asked to do something with another individual. This response usually indicates that the person is unwilling or unable to confirm their participation with the other individual, or just doesn't want to participate and doesn't like telling people "no thanks".
Example 1:
Person A: "Hey Mac, want to go to the movies tonight?"
Person B: "I'm not really sure what I'm doing tonight, but I'll see what's up!"
Example 2:
Person A: "Hey Mac, we are going to the bar tonight. Want to join?"
Person B: "Yea, I'll see what's up..."