Rb4 is a peptide derived from the N-terminal of proteolipid protein 2 (PLP2), a transmembrane lipoprotein first identified in human colonic epithelial cells. Rb4 triggers necrotic cell death in murine melanoma mainly through ER stress caused by inhibition of SERCA transporter activity, which leads to alteration of actin dynamics and RIP1 inhibition. Rb4 acts directly on tumour cells to induce the expression of two damage associated molecular pattern (DAMP) molecules, HMGB1 and calreticulin, which triggers an immunoprotective response against melanoma cells. In vivo Rb4 reduces lung metastasis of tumour cells and delays subcutaneous melanoma growth.
