Learn Italian: Perché mi accusi? Io non c'entro niente. - Why do you accuse me? I have nothing to do with it.

It comes from the pronominal verb entrarci (entrare + the particle ci). While entrare means "to enter", adding ci gives it the figurative meaning of "to fit into this matter" or "to be involved". English uses "to have something to do with it", but Italian literally expresses whether someone or something "enters into it" or not.

Why use niente here? Could I just say io non c'entro?

Yes, you can simply say non c'entro ("I am not involved"), but adding niente is extremely common for emphasis. Italian requires double negatives here, so non and niente work together to mean "I have absolutely nothing to do with it."

Since Italian normally drops subject pronouns, why is Io explicitly used in this sentence?

It creates a strong contrast with the first half of the sentence. The speaker is emphasizing themselves defensively: "Why accuse me? I have nothing to do with it." Dropping Io would be grammatically fine but would lose this punchy, defensive contrast.

The lesson focuses on the negative, but can I use entrarci affirmatively to say something is relevant?