ALPK1 (alpha-kinase 1) is a cytosolic pattern recognition receptor that detects bacterial pathogen-associated molecular patterns (PAMPs) and initiates innate immune responses 1. Specifically, ALPK1 recognizes and binds ADP-D-glycero-β-D-manno-heptose (ADP-heptose), a metabolite present in Gram-negative and some Gram-positive bacteria, with stronger responses to related heptose derivatives 2. ADP-heptose binding stimulates ALPK1's serine/threonine kinase activity to phosphorylate and activate TIFA, triggering pro-inflammatory NF-κB signaling 3. This pathway has significant disease relevance: gain-of-function ALPK1 mutations cause ROSAH syndrome (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, headache), a recognized autoinflammatory condition 3. Additionally, bacterial ALPK1 activation promotes colorectal cancer pathogenesis via increased IL-8 and anti-apoptotic gene expression 4, and drives metastasis by inducing ICAM1 expression on endothelial cells 5. Clinically, ADP-heptose accumulation with aging promotes clonal hematopoiesis of indeterminate potential (CHIP) expansion 6. ALPK1 agonists show promising therapeutic potential in cancer immunotherapy and hepatitis B treatment 78.