RIPK4 (receptor-interacting serine/threonine kinase 4) is a multifunctional kinase with distinct roles in development, homeostasis, and disease. Primarily, RIPK4 regulates epidermal differentiation through activation of LATS1/2 in the Hippo pathway via phase separation mechanisms, with inactivating mutations causing developmental syndromes with defective epidermal differentiation 1. RIPK4 also controls skeletal homeostasis by phosphorylating MFN2, promoting mitochondrial fragmentation that drives osteogenesis while restricting myelopoiesis through mitochondrial transfer regulation 2. Mechanistically, RIPK4 kinase activity is essential for ferroptotic cell death in response to oxidative stress, operating through downregulation of ACSM1 and modulation of polyunsaturated fatty acid metabolism 3. RIPK4 protein stability is regulated by GSK3Ξ²-mediated phosphorylation and UCHL3-dependent deubiquitination 4. Clinically, RIPK4 exhibits contradictory roles in cancer. In cutaneous squamous cell carcinoma, RIPK4 depletion paradoxically increases malignancy potential 5, while RIPK4 overexpression promotes ovarian cancer progression through epithelial-mesenchymal transition and invasion 6. BRAF kinase inhibitors reduce RIPK4 levels in melanoma cells 7. Notably, RIPK4 and RIPK1-3 remain understudied in neuroinflammation despite their importance in other RIPK family functions 8.
No tissue expression data available for this gene.