Nitric Oxide Synthase 1 Adaptor Protein (NOS1AP, previously named CAPON) was firstly identified in the rat brain in 1998, and its SNP rs12742393 was associated with type 2 diabetes (T2D). Structurally, NOS1AP consists of a phosphotyrosine-binding (PTB) domain at its N-terminal and a PDZ (PSD-95/discs-large/ZO-1) ligand motif at its C-terminal. The PTB domain of NOS1AP mediates the interactions with Dexras1, scribble, and synapsins. The PDZ ligand motif of NOS1AP binds to the PDZ domain of NOS1, the enzyme responsible for nitric oxide synthesis in the nervous system. NOS1AP is implicated in Dexras1 activation, neuronal nitric oxide production, Hippo pathway signaling, and dendritic development through the association with these important partners. An increasing body of evidence is pointing to the significant roles of NOS1AP in excitotoxic neuronal damage, traumatic nervous system injury, bipolar disorder, and schizophrenia.