Src-kinase associated protein 2 (SKAP2) is an intracellular scaffolding protein widely expressed in immune cells. It is involved in multiple downstream signalling pathways, especially integrin signalling. SKAP2 binds to various partners, fine-tunes cytoskeleton rearrangement, and thus regulates cell migration and immune cell function. Mutations in SKAP2 are associated with inflammatory disorders like Type 1 Diabetes and Crohn's disease [1].

In gene knockout studies, Skap2-/-mice had a 100-fold higher bacterial burden during K. pneumoniae pulmonary infections as SKAP2-dependent signalling in neutrophils is essential for K. pneumoniae-activated ROS production and bacterial clearance [3]. SKAP2 knockout also increased the severity of colitis and tumorigenesis in a mouse model of tumorigenesis with colitis, as it prevents excess inflammation by inhibiting the TLR4-NF-κB pathway and activates the TLR4-IFNβ pathway through SHP-1 and SHP-2 [2]. In addition, knockdown of SKAP2 in INS-1E cells and primary rat β-cells aggravated cytokine-induced apoptosis, suggesting an anti-apoptotic function of SKAP2 in relation to Type 1 Diabetes [4].

In conclusion, SKAP2 is crucial for immune cell-related functions such as pathogen clearance, regulation of inflammation, and control of β-cell apoptosis. Gene knockout mouse models have revealed its significant roles in diseases including infectious diseases, colitis-associated cancers, and Type 1 Diabetes, providing valuable insights into the underlying mechanisms and potential therapeutic targets.