Prolactin (PRL) is a neuroendocrine hormone that is closely related to growth hormones and more distantly related to the peptide hormones of the interleukin family. The endocrine effects of PRL on human breast tissues include the regulation of growth and differentiation of ductal epithelium, proliferation and differentiation of lobular units, and initiation and maintenance of lactation. PRL and growth hormone receptors are members of the cytokine receptor superfamily. Both the PRLr and growth hormone receptors are single-chain transmembrane proteins composed of extracellular, transmembrane, and intracellular domains. Prolactin modulates immune system function by stimulating the proliferation and survival of cells through its receptor, present on T and B lymphocytes and macrophages. The function of PRL is mediated by a variety of signaling cascades as well as by the wide variety of PRLr isoforms observed in nature. A long form and several other isoforms are expressed in human tissues. The nucleotide sequence of the novel intermediate isoform of PRLr is identical to the long isoform, except for a 573-base pair deletion occurring at a consensus splice site, resulting in a frameshift and truncated intracytoplasmic domain. The long isoform of PRLr is N-glycosylated. As the extracellular domain of the intermediate isoform is identical to that of the long isoform, glycosylation patterns are assumed to be similar. Using immunohistochemical analysis, PRLr expression has been observed in 95% of both normal and malignant breast epithelium; no correlation between PRL expression and ER-PR status has been established.