Mutations of 19 different genes can account for MSMD: CYBB, IFNG, IFNGR1, IFNGR2, IL12B, IL12RB1, IL12RB2, IL23R, NEMO, SPPL2A, and TBX21 for isolated MSMD; ISG15, JAK1, RORC, TYK2, USP18 and ZNFX1 for syndromic MSMD; and IRF8, STAT1, and TYK2 for isolated or syndromic MSMD depending on the mutation4,6–8,10. Here, USP18 is linked to Mendelian susceptibility to mycobacterial diseases.