Cation diffusion facilitators (CDFs) are transmembrane proteins that provide tolerance of cells to divalent metal ions, such as cadmium, zinc, and cobalt. These proteins are considered to be efflux pumps that remove these divalent metal ions from cells.[1][2] However, some members of the CDF superfamily are implicated in ion uptake.[3] All members of the CDF family possess six putative transmembrane spanners with strongest conservation in the four N-terminal spanners.[4] The Cation Diffusion Facilitator (CDF) Superfamily includes the following families:[4][5]