Dysfunction of phospholipase Cγ in immune disorders and cancer

•New evidence for disease-linked mutations in phospholipase Cγ (PLCγ).•The molecular mechanism of dysfunction involves impact on autoinhibition. The surge in genetic and genomic investigations over the past 5 years has resulted in many discoveries of causative variants relevant to disease pathophysiology. Although phospholipase C (PLC) enzymes have long been recognized as important components in intracellular signal transmission, it is only recently that this approach highlighted their role in disease development through gain-of-function mutations. In this review we describe the new findings that link the PLCγ family to immune disorders and cancer, and illustrate further efforts to elucidate the molecular mechanisms that underpin their dysfunction.