IL3RA encodes the interleukin-3 receptor alpha subunit, a cell surface receptor expressed on hematopoietic progenitor cells, monocytes, B lymphocytes, and myeloid cells 1. Upon ligand stimulation, IL3RA heterodimerizes with IL3RB and activates JAK2 and PI3K signaling, leading to STAT5-mediated transcriptional programs that control hematopoietic cell proliferation and differentiation 2. IL3RA is located in the X-Y pseudoautosomal region 3. IL3RA plays critical roles in immune pathology. In multiple sclerosis, IL3RA expression on CNS myeloid cells mediates IL-3 signals from astrocytes and infiltrating T cells, promoting immune cell chemotaxis and CNS infiltration that exacerbates disease severity 4. In allergic responses, IL-3 acts on IL3RA+ sensory neurons through JAK2-STAT5 signaling to lower allergen activation thresholds and initiate allergic immunity 2. Clinically, IL3RA overexpression is a hallmark of blastic plasmacytoid dendritic-cell neoplasm (BPDCN), an aggressive hematologic malignancy. Tagraxofusp, an IL-3-diphtheria toxin fusion protein targeting CD123 (IL3RA), achieved 72% complete response rates in untreated BPDCN patients 5. IL3RA overexpression also characterizes specific acute myeloid leukemia subgroups with worse prognosis, representing therapeutic targets for CD123-directed therapies 6.