For example, the phospho-mimetic S25D mutation prevented the reported apoptosis-driven skin lesions and necroptosis-driven splenomegaly caused by lack of SHARPIN expression, as demonstrated by macroscopic analysis and staining of tissue sections with H&E, TUNEL (cell death) and cleaved Caspase-3 (apoptosis) (Fig. 4d), and by the weight of the spleens (Fig. 4e). This evidence concerns the gene SHARPIN and Splenomegaly.