Nck-associated protein 1-like

NCKAP1L (Nck-associated protein 1-like) is a 1127-amino acid protein that functions as a hematopoietic-specific regulator of the actin cytoskeleton (UniProt: P55160). It serves as a component of the WAVE2 complex, which signals downstream of RAC to stimulate F-actin polymerization and controls lymphocyte development, activation, and migration, as well as phagocytosis in neutrophils and macrophages. In T-cells, NCKAP1L regulates mTORC2-dependent AKT phosphorylation and cytokine secretion.

NCKAP1L is primarily associated with immune system function and hematopoietic cell regulation. Biallelic mutations cause Immunodeficiency 72 with autoinflammation and lymphoproliferation (IMD72), characterized by recurrent infections, lymphoproliferation, and autoimmune manifestations (UniProt: P55160, MIM 618982).

NCKAP1L is elevated in Alzheimer's disease brain tissue. According to Chaparral AD proteomics analysis of post-mortem AD brain versus age-matched controls, NCKAP1L is significantly upregulated with a mean log2 fold-change of 0.89 (Chaparral AD proteomics). This upregulation was detected across the TMT-labeled quantitative proteomics experiment examining four subcellular fractions, suggesting a potential role in AD pathology or neuroinflammatory responses.