Ski, also known as Sloan-Kettering Institute protein, is an evolutionarily conserved protein involved in diverse cellular processes. It acts as both an oncoprotein and tumor suppressor gene, mediating cell proliferation, differentiation, metastasis, and invasion in various cancers [1]. Ski is also implicated in regulating key signaling pathways such as the TGFβ pathway [2].

Loss-of-function studies have provided insights into Ski's role. Loss of one copy of mouse ski increases susceptibility to tumorigenesis in mice, while its overexpression is associated with cancer progression in human melanoma, esophageal, breast, and colon cancers [3]. In Th17-related diseases, SKI expression suppresses pathogenic Th17 cell response. Ectopic SKI expression in T cells prevented experimental autoimmune encephalomyelitis, an animal model of human multiple sclerosis [4].

In conclusion, Ski plays dual roles in cancer development, and its dysregulation is associated with tumorigenesis and cancer progression. In addition, Ski is crucial in regulating pathogenic Th17 cell-related autoimmune diseases. The use of mouse models in these studies has significantly enhanced our understanding of Ski's functions in disease, providing potential targets for therapeutic intervention.