HOIL-1 / HOIP deficiency is a rare inherited, autosomal recessive deficiency of the human HOIL-1 gene. HOIL-1 is 1 of 3 proteins in the linear ubiquitin chain assembly complex (LUBAC) involved in tagging proteins for degradation and cellular trafficking. Deficiency of this gene alters signaling in the NF-kb pathway in fibroblasts, leading to delayed or altered inflammation with impaired fibroblast response to immune signals, impaired cytokine responses, and impaired B and T lymphocytes. Conversely, monocytes affected by this mutation have increased sensitivity to immune markers. There have been very few reported cases of HOIL-1 / HOIP deficiency.

Clinically, HOIL-1 / HOIP deficiency manifests as chronic autoinflammation, combined immunodeficiency, recurrent invasive pyogenic infections, and muscular amylopectinosis (intracellular glycogen deposits in cardiac, smooth, or skeletal myocytes) and lymphangiectasias in various organs. Reported infections include methicillin-resistant Staphylococcus aureus abscesses, herpes simplex virus meningitis, pneumococcal sepsis, Candida esophagitis, Haemophilus influenzae meningitis, Escherichia coli sepsis and pyelonephritis, Giardia intestinalis sepsis, cytomegalovirus viremia / pneumonitis, and Candida albicans sepsis.

HOIL-1 / HOIP deficiency typically presents in infancy, with recurrent infections that progress in severity over time.

HOIL-1 / HOIP deficiency is a potentially fatal disease due to complications related to heart failure secondary to amylopectinosis of the myocardium.