PICK1 (protein interacting with PRKCA 1) is a PDZ and BAR domain-containing scaffold protein that regulates subcellular localization and trafficking of membrane proteins, particularly AMPA glutamate receptors 1. The protein's PDZ domain binds to membrane proteins with type II PDZ-binding motifs, while its BAR domain interacts with phosphoinositides, enabling PICK1 to couple membrane proteins to trafficking machinery 1. PICK1 plays crucial roles in synaptic plasticity by regulating AMPA receptor surface expression and internalization, which is central to chr22 pain pathophysiology through maladaptive synaptic changes 2. The protein has clinical significance in multiple contexts: mutations in PICK1 cause globozoospermia, a form of male infertility characterized by round-headed sperm 3, and genetic variants near PICK1 are associated with obesity in genome-wide association studies 4. Recent research demonstrates that PICK1 can be epigenetically silenced through DNA methylation, which enhances macrophage efferocytosis and provides cardioprotection in myocardial infarction 5. PICK1 has also been implicated as a candidate schizophrenia susceptibility gene 6. These diverse functions highlight PICK1's importance in neuroplasticity, reproduction, metabolism, and psychiatric disorders.