Histidine decarboxylase (HDC) is a pyridoxal phosphate-dependent enzyme that catalyzes histamine biosynthesis from the amino acid histidine 1. HDC is expressed in mast cells, basophils, brain neurons (particularly in the hypothalamic tuberomammillary nucleus), and stomach cells 23. The enzyme's expression is tightly regulated by transcription factors GATA2 and MITF, which bind to enhancer elements upstream of the HDC gene to control transcription 4. The GC box within the proximal HDC enhancer is critical for gene expression and is essential for zinc finger transcription factor binding 2. Clinically, HDC function is central to IgE/mast cell-mediated anaphylaxis, as deletion of regulatory elements or transcription factors abolishes anaphylactic responses 24. Rare mutations in HDC are associated with Tourette syndrome, and HDC-knockout mice recapitulate tic-like behavioral abnormalities and neurochemical changes observed in patients 5. In narcolepsy type 1, histamine neuron populations expressing HDC show a 36% increase in number, suggesting compensatory upregulation of wake-promoting histaminergic systems 3. These findings establish HDC as a crucial enzyme linking histamine metabolism to immune responses, neurological function, and sleep-wake regulation.