NOD2 and inflammatory bowel disease: Here, we report a novel XLP-2-causing mutation in the XIAP BIR1 domain, leading to a premature stop codon and a loss of protein expression, which results in impaired lymphocyte apoptosis and NOD2-dependent signalling with clinical manifestations that include a complicated course of IBD, unresponsiveness to standard treatment, including biologics (infliximab and vedolizumab) and relapsing HLH.