ANTXR2 (Anthrax Toxin Receptor 2) functions as a cell surface receptor that facilitates cellular entry of Bacillus anthracis toxins. The protein binds to the protective antigen (PA) component of anthrax toxin, leading to heptamerization of the receptor-PA complex 1. Following binding, the complex relocates to lipid rafts and undergoes clathrin-dependent internalization, ultimately forming endosomal pores that allow toxin components to escape into the cytoplasm 1. Beyond its role in microbial infection, ANTXR2 has significant disease relevance. Mutations in ANTXR2 cause hyaline fibromatosis syndrome, including severe forms like infantile systemic hyalinosis, characterized by tissue accumulation of hyaline substances 2. Interestingly, ANTXR2 is highly expressed in dorsal root ganglion sensory neurons, where anthrax toxins can modulate pain signaling through protein kinase A pathways, suggesting potential therapeutic applications 3. Additionally, ANTXR2 polymorphisms show weak associations with ankylosing spondylitis, though results vary across populations 45. Clinical significance includes its role as a genetic biomarker for fibromatosis syndromes and potential target for engineered pain therapeutics, though knockout studies suggest it may not be causally related to hypertension despite genetic associations 6.