Cytoskeleton-associated protein 4: a double-edged sword in cell growth and aging

Cytoskeleton-Associated Protein 4 (CKAP4) is a multifunctional protein implicated in diverse cellular processes, including cytoskeletal organization, signal transduction, and extracellular matrix remodeling. Recent studies have highlighted the dual role of CKAP4 in regulating cell growth and aging. On one hand, CKAP4 can promote cell proliferation and survival by activating signaling pathways such as PI3K/Akt, thereby delaying cellular senescence under physiological conditions. On the other hand, under chronic stress or pathological stimuli, CKAP4 may induce cell cycle arrest and accelerate aging by interacting with ligands such as antiproliferative factor (APF) and Dickkopf-1 (DKK1), leading to the upregulation of cell cycle inhibitors and the suppression of autophagy. Moreover, CKAP4 has emerged as a key mediator linking extracellular matrix remodeling to inflammatory responses, which are closely associated with age-related diseases. This review comprehensively summarizes the current understanding of CKAP4's molecular mechanisms in cell longevity and aging, discusses its involvement in inflammation and tissue homeostasis, and explores its potential as a therapeutic target for aging-related disorders.