Multifunctional Proteins and Alternative Translation: Functional Diversification of BetaA3/A1-Crystallin Via Leaky Ribosomal Scanning

βA3/A1-crystallin is a multifunctional protein that is expressed in a number of ocular cells and tissues: lens, retinal pigment epithelium (RPE), retinal astrocytes, and ganglion cells. Its function is very context- and cell-specific, ranging from maintaining the structural integrity of the lens to mediating lysosomal clearance and phosphoinositide metabolism in the RPE. In addition to being a classical moonlighting protein (when one polypeptide chain exhibits more than one function), the functional diversity of βA3/A1-crystallin is also shaped by alternative translation. In mammals, two isoforms—βA3- and βA1-crystallins—are produced from the same mRNA via the process of leaky ribosomal scanning. Our recent findings suggest that these isoforms are functionally different, and that their functions are also cell- and context-dependent. In this chapter, we review the most recent findings on the evolution and functional diversity of βA3/A1-crystallin and discuss the significance of this multifunctional protein for ocular translational research.