Prokineticins are family of small proteins involved in many important biological processes including food intake and control of energy balance. The prokineticin 2 (PROK2) is expressed in several peripheral tissues and areas in the central nervous system. PROK2 activates G protein-coupled receptors, namely, prokineticin receptor 1 (PROKR1) and prokineticin receptor 2 (PROKR2). Preclinical models exhibiting disturbances of the PROK2 pathway (at the level of PROK2 or its receptors) are characterized by changes in food intake, feeding behavior and insulin sensitivity related to a dysfunction of the energy balance control. In Humans, mutations of PROK2 and PROKR2 genes are associated to the Kallmann syndrome (KS) that affects both the hormonal reproductive axis and the sense of smell and may also lead to obesity. Moreover, plasma PROK2 concentration has been correlated with various cardiometabolic risk factors and type 2 diabetes (T2D). The present review summarizes knowledge on PROK2 structure, signaling and function focusing on its role in control of food intake and energy homeostasis. Copyright © 2021. Published by Elsevier B.V.