Among the about 20,000 genes in the human proteome there are still many rather unknown but potentially interesting proteins that deserve some extra attention. Here we will focus on RD3L, a less investigated gene related to the Retinal Degeneration Protein 3 (RD3).

RD3 is a well-known protein, specifically expressed in photoreceptor cells in the eye, that plays a critical role in the regulation of guanylate cyclase signaling and photoreceptor cell survival. Genetic defects or mutations in RD3 produce a non-functional truncated protein that drives early-onset photoreceptor degeneration in patients with Leber Congenital Amaurosis.

The RD3-like gene (RD3L) is related to RD3 but much less investigated and without evidence at protein, transcript, or homology levels in UniProt. That this protein deserves more attention is however strongly suggested when looking at the data in the Human Protein Atlas. The expression profiles in both bulk and single cell RNA seq show specific expression in retina and heart muscle and more specifically in photoreceptor cells, bipolar cells, horizontal cells and cardiomyocytes. This suggest a role also for this protein in the eye, but also perhaps more surprisingly in the heart.

Expression clustering and correlation of bulk tissue and single cell RNA seq data further show RD3L to cluster together with other genes known to be related to both heart development and neuronal signaling in the context of horizontal and bipolar cells .

So far RDL3 has not been analysed by immunohistochemistry in retina, but analysis of the heart muscle confirms these findings by showing specific staining in the the intercalated discs of cardiomyocytes.