Biallelic loss-of‐function variants in ISG15 were initially described in the context of patients with Immunodeficiency 38 (OMIM: 616126), an AR disorder which confers syndromic Mendelian susceptibility to Mycobacterial diseases (MSMD) and affects about 1 in 50,000 individuals exposed to environmental mycobacteria or BCG vaccine strains [4]. This evidence concerns the gene ISG15 and Mendelian susceptibility to mycobacterial diseases.