The cone-rod homeobox protein CRX, encoded by CORD2 is a transcription factor proposed as a regulator of photoreceptor differentiation, normal retina development, and pineal function. CRX is expressed in uncommitted proliferating cells and cells committed to the bipolar lineage in as early as 10.5 weeks gestation in the developing human eye. Mutations in CORD2 are associated with retinal degenerative diseases including cone-rod dystrophies and Leber congenital amaurosis, a disorder of the retina resulting in severe visual impairment. In the mature eye, CRX is highly expressed in photoreceptor cells while moderately in bipolar cells.

Elevated and extensive nuclear CRX expression was observed in all retinoblastoma cell lines and >95% of retinoblastoma cells. CRX was identified in undifferentiated regions as well as rosettes and flerettes, which are features of tumor differentiation. Additionally, nuclear CRX staining was also observed in >90% pineal parenchymal tumors. CRX was reported as a sensitive and specific marker for retinoblastoma and pineal parenchymal tumors when used as part of a panel comprising of Synaptophysin and GFAP.