However these cells are dramatically expanded in individuals with some immune dysregulatory conditions, such as ALPS due to genetic variants affecting the FAS/FASL pathway (Bleesing et al., 2001; Dowdell et al., 2010; Fisher et al., 1995; Maccari et al., 2021; Magerus-Chatinet et al., 2009; Völkl et al., 2016), or in patients with heterozygous STAT3 GOF (Flanagan et al., 2014; Haapaniemi et al., 2015; Milner et al., 2015; Nabhani et al., 2017) or homozygous PDCD1 (PD-1) (Ogishi et al., 2021) variants. The gene discussed is PDCD1; the disease is autoimmune lymphoproliferative syndrome.