Mammalian TRP channels display heterogenous biophysical properties and are involved in a variety of signal transduction pathways. To carry out their diverse biological functions and to adapt these functions to changes of the environment, mechanisms to regulate their molecular structure are required. Transcriptional regulation and post-transcriptional RNA processing represent essential instruments to generate TRP channel variants with modified properties. TRP variants are expressed depending on the tissue and developmental state. They can show distinct biophysical properties and mechanisms of activation, and thereby determine channel function and malfunction in certain human diseases. In this review, we give an overview of the variants of a given TRP gene, with the focus on the TRPM subfamily, and discuss their relevance with respect to their function under physiological and pathological conditions.