TRPM1 proteins are necessary for the transduction current in retinal ON-bipolar cells and their dysfunction results in congenital stationary night blindness (CSNB). TRPM1 belongs to the large family of TRP cation channels and is highly homologous to TRPM3, TRPM6 and TRPM7. The analysis of the ionic permeabilities of these channels indicated that all of these four proteins, including TRPM1, form divalent permeable cation channels. However, while TRPM3, TRPM6 and TRPM7 are well permeated by zinc ions, TRPM1 is not and actually is inhibited by extracellular zinc ions in the low micromolar range. Given the high homology between TRPM1 and TRPM3, we were interested in elucidating the structural basis for the different response to zinc application. We first determined that the zinc permeability or zinc inhibition are pore properties that can be transferred to the other channels by pore transplantation. The most prominent difference between TRPM1 and TRPM3 in the pore region is a short stretch of 7 amino acids (LYAMEIN motif). Using mutagenesis and subsequently patch-clamp electrophysiology we found that this short motif is the key determinant of the zinc inhibition. Removing the LYAMEIN motif from the pore of TRPM1 proteins rendered them zinc permeable, while addition of the LYAMEIN motif to the pore of TRPM3 yielded channels that were susceptible to inhibition by extracellular zinc ions. Our results indicate that the divalent permeation properties of the TRPM channel pore can be fine tuned with high precision to distinguish between different divalent cations and to thereby attain various selectivity profiles.