The 'ether-a-go-go-related' gene type 1 (ERG1 or Kv11.1) protein is the product of the KCNH2 gene. Currents generated by ERG1 channels are important in a range of tissues including neuronal, smooth muscle, and cardiac tissues, as well as in cancer cells. There are five known isoforms of the ERG1 protein. Overlapping patterns of endogenous expression of ERG1 isoforms have been described in several tissue types. Abnormal changes in the relative abundance of ERG1 isoforms may result in disease. Recent studies have suggested that the different isoforms play a prominent role in expression and trafficking of ERG1 channels as well as in modulating the electrophysiological properties of the channels. This review focuses on the differences between the ERG1 isoforms and describes the physiological implications thereof. It is described how changes in the relative expression level of the isoforms may have significant physiological consequences by modulation of tissue excitability. Additionally, the review proposes a standardized nomenclature of ERG1 isoforms based on their structural features.