Cerebellar degeneration-related protein 2 (CDR2)

Cerebellar degeneration-related protein 2 (CDR2) is an **intracellular onconeural antigen** primarily expressed in cerebellar Purkinje cells, brainstem neurons, and testes under physiological conditions, but ectopically expressed in some breast and ovarian tumors[2][6][7][8]. It is the principal antigen recognized by anti-Yo antibodies, which are highly specific for paraneoplastic cerebellar degeneration (PCD), an autoimmune syndrome induced by tumor-driven immune responses that attack neuronal tissue[6][8]. CDR2 localizes to the nucleus in Purkinje cells, where it interacts with proteins involved in **RNA processing and transcriptional regulation** (notably nuclear speckle proteins such as SON and serine/arginine-rich splicing factors)[1][3]. In the context of cancer, aberrant CDR2 expression in tumor cells triggers an anti-tumor immune response which cross-reacts with neurons, leading to T cell–mediated neuronal loss and, less commonly, direct antibody-mediated cytotoxicity[6][8]. The presence of anti-Yo (anti-CDR2) antibodies in cancer patients is a diagnostic marker for PCD but does not directly inform about a druggable target or mechanism of action for therapeutic drugs, as CDR2 is not currently a therapeutic target[2][5][7][8].

Other names

CDR62YoMajor Yo paraneoplastic antigenParaneoplastic cerebellar degeneration-associated antigenYo paraneoplastic antigenPCD17