The prolactin receptor (PRLR) is a transmembrane protein belonging to the class I cytokine receptor superfamily, widely expressed in mammary gland, reproductive organs, liver, and brain. Signal activation is initiated when a single prolactin (PRL) molecule binds to this pre-dimerized PRLR, inducing a specific conformational change. This triggers the associated JAK2 kinases to phosphorylate each other and the receptor, ultimately leading to the recruitment and activation of downstream STAT5 transcription factors. This precise mechanism governs essential physiological processes, including lactation, reproduction, metabolism, and immune function, and its dysregulation is implicated in diseases such as certain cancers and endometriosis.