Nitric oxide synthase 1 adaptor protein (NOS1AP)

Nitric oxide synthase 1 adaptor protein (NOS1AP), also known as CAPON, is a cytosolic adaptor and scaffold protein encoded by the NOS1AP gene[1][3]. NOS1AP binds to neuronal nitric oxide synthase (nNOS) via a C-terminal PDZ-binding domain and interacts with other proteins such as Dexras1, synapsins, and polarity proteins, making it pivotal for the spatial regulation of nNOS signaling in neurons and various tissues[1][2][3][5]. In the heart, NOS1AP regulates myocardial repolarization and modulates risk for arrhythmias via effects on L-type calcium channels and nNOS activity[3][4]. In the central nervous system, NOS1AP impacts NMDA receptor-nNOS signaling, dendrite formation, and synaptic plasticity; genetic variations are linked to susceptibility to schizophrenia, depression, PTSD, and other psychiatric conditions[3][5]. NOS1AP is also implicated in cell migration in cancer and cytoskeletal dynamics in renal podocytes[3][4]. It is currently recognized as a promising therapeutic target in cardiovascular and neuropsychiatric diseases, though no direct drug therapies currently exist; genetic variants impact drug response and serve as biomarkers for patient stratification[3][4][5].

Other names

Carboxyl-terminal PDZ ligand of neuronal nitric oxide synthase proteinCAPONKIAA0464C-terminal PDZ ligand of neuronal nitric oxide synthase proteinC-terminal PDZ domain ligand of neuronal nitric oxide synthase6330408P19RikNPHS22Nitric oxide synthase 1 (neuronal) adaptor proteinLigand of neuronal nitric oxide synthase with carboxyl-terminal PDZ domain

Drug candidates targeting the nNOS:NOS1AP interaction may inhibit or modulate nNOS/PSD95/NMDA receptor signaling to block excitotoxicity, cell death, or pathological synaptic remodelling[5]. Variants may modulate myocardial response to calcium channel blockers (pharmacogenomic effect)[3].