MARCKS (myristoylated alanine rich protein kinase C substrate) is a membrane-associated protein that plays crucial roles in cytoskeletal organization and cellular signaling. The protein regulates actin filament organization and serves as a bridge between calcium/calmodulin and protein kinase C signaling pathways 1. MARCKS sequesters phosphatidylinositol 4,5-bisphosphate (PIP2) at plasma membrane lipid rafts in quiescent cells, which is reversed by protein kinase C activation 1. Mechanistically, MARCKS functions through calmodulin-dependent translocation that can activate the PI3K/AKT/mTOR pathway 2. The protein requires proper N-myristoylation for its cellular function, as demonstrated by altered MARCKS myristoylation in ACBD6-deficient models 3. MARCKS has significant disease relevance, being implicated in cancer progression and metastasis, particularly in gastric cancer peritoneal metastasis where it marks high-plasticity cancer clusters with poor prognosis 4. In prostate cancer, MARCKS serves as part of a prognostic signature for biochemical recurrence 5. The protein also contributes to hypertension regulation, as human alpha-1 antitrypsin treatment reduces MARCKS expression alongside blood pressure reduction in diabetic mice 6. Additionally, MARCKS is co-regulated with APOE in brain cells and linked to Alzheimer's disease pathogenesis 7.