Protein kinase C and casein kinase substrate in neurons protein 2

PACSIN2 (Protein kinase C and casein kinase substrate in neurons protein 2) is a lipid-binding protein that regulates caveolar morphogenesis and endocytosis (UniProt: Q9UNF0). It promotes tubulation of phosphatidic acid-containing membranes and facilitates intracellular vesicle transport, including endocytosis of cell-surface receptors such as the EGF receptor. The protein also plays roles in endothelial cell polarity and angiogenesis by recruiting associated factors to adherens junctions.

PACSIN2 is expressed in neurons and endothelial tissues where it mediates membrane dynamics and receptor trafficking. Beyond physiological roles, it enhances HIV-1 cell-to-cell spread and facilitates bacterial pathogen dissemination, suggesting broader involvement in membrane remodeling processes.

In Alzheimer's disease, PACSIN2 is upregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics), with a mean log2 fold-change of +0.33 across subcellular fractions. This upregulation may reflect compensatory or pathological changes in endocytic and membrane trafficking pathways relevant to amyloid-β processing or clearance in AD neurodegeneration.