The transient receptor potential melastatin 6 (TRPM6) is a magnesium-permeable ion channel critical for systemic magnesium homeostasis. It is predominantly expressed in the kidney and intestine, where it facilitates epithelial magnesium reabsorption and absorption. TRPM6 mutations are linked to hereditary hypomagnesemia, underscoring its role in magnesium balance. TRPM6 antibodies are essential tools for studying the protein’s expression, localization, and function. These antibodies are commonly used in techniques like Western blotting, immunohistochemistry (IHC), and immunofluorescence (IF) to detect TRPM6 in tissues or cell lines. Given its structural complexity—a fusion of an ion channel domain and an α-kinase domain—TRPM6 antibodies must specifically target unique epitopes to avoid cross-reactivity with homologous proteins like TRPM7. Research using TRPM6 antibodies has advanced understanding of magnesium-related disorders, including hypomagnesemia, hypertension, and diabetes. Additionally, they aid in exploring TRPM6’s interplay with hormones (e.g., estrogen, insulin) and its regulation by dietary magnesium. Commercial TRPM6 antibodies are typically raised against peptide sequences in the kinase or channel regions, with validation in knockout models to confirm specificity. Challenges remain in ensuring antibody reliability across experimental conditions, emphasizing the need for rigorous validation in studying TRPM6’s pathophysiological roles.