SELENOK (selenoprotein K) is an endoplasmic reticulum-resident selenoprotein with multifaceted roles in cellular homeostasis and immune regulation. Its primary function involves protein palmitoylation, where it stabilizes the palmitoyltransferase DHHC6 to facilitate palmitoylation of key substrates including CD36, GluA2, ITPR1, and TfR-1 1. This palmitoylation activity regulates protein trafficking, localization, and function across multiple pathways. Mechanistically, SELENOK participates in endoplasmic reticulum-associated degradation (ERAD) of misfolded proteins and modulates calcium flux in immune cells 1. Additionally, SELENOK enhances STING oligomerization to facilitate antiviral innate immune responses 2, while protecting cells from ER stress-induced apoptosis and oxidative stress. Clinically, SELENOK demonstrates significant neuroprotective potential in Alzheimer's disease. SELENOK deficiency impairs microglial amyloid-beta phagocytosis through reduced CD36 palmitoylation, exacerbating cognitive deficits in 5xFAD mice, whereas SELENOK overexpression reverses these effects 3. Similarly, SELENOK regulates GluA2 palmitoylation to promote AMPA receptor assembly and restore synaptic plasticity in AD models 4. SELENOK also protects against iron dyshomeostasis-related neurodegeneration by maintaining TfR-1 palmitoylation and mitochondrial function 5. In cancer contexts, SELENOK knockdown induces ferroptosis in cervical cancer cells 6, and elevated SELENOK expression correlates with improved melanoma prognosis through enhanced immune infiltration 7.