The most prominent members of the interleukin-1 (IL-1) superfamily are IL-1α and IL-1β. They lack a signal peptide and are secreted by an unconventional, endoplasmic reticulum-Golgi-independent mechanism. IL-1α was reported to be more widely and constitutively expressed and has intracellular functions, but also acts locally in a membrane-bound form by activating IL-1R1. Additionally, passive release of IL-1α upon cell death can trigger a sterile inflammatory response to dying cells. The cleavage of IL-1α is not mediated by caspase-1 and is not required for binding to IL-1R1. Recently it has been observed that all activators of the inflammasome NLRP3/NALP3 induce the simultaneous secretion of IL-1α and IL-1β. Although most activators fully rely on the inflammasome for IL-1α secretion, some induce the processing and secretion of IL-1α in an inflammasome-independent manner.