In particular, most of the substitutions and small deletions in these isozymes that are linked to cancers (Burger et al., 2016; Kataoka et al., 2015; Woyach et al., 2014) or autoimmune disease (Ombrello et al., 2012) occur at the interfaces between the core and regulatory domains based on the structure of autoinhibited PLC-γ1. Here, PLCG1 is linked to autoimmune disease.