The two lens structure proteins, αA-Crystallin (HspB4) and αB-Crystallin (HspB5), control apoptosis through regulation of multiple signaling transduction pathways

α-Crystallins are major lens structural proteins, belonging to the family of the small heat shock proteins (HSPs). α-Crystallins consist of two polypeptides, αA and αB that share 55% amino acid sequence identity. The two 20-kDa subunits form soluble aggregates with an average molecular mass of 600-800 kDa and can be isolated from lens fiber cells as a heteroaggregate containing αA- and αB-peptides in a ratio of 3 to 1. αAcrystallin (HspB4) is predominantly expressed in the ocular lens with small amounts present in spleen and thymus. In contrast, αB-crystallin (HspB5) is expressed mainly in the lens but also expressed outside of the lens in a number of tissues such as skeletal and cardiac muscle and to lesser extent in skin, brain, and kidney. Besides their structural role, α-crystallins are important chaperones in the ocular lens, act as autokinases, and also play important roles in suppressing both developmental and stress-induced apoptosis to guard the lens differentiation and prevent pathogenesis in the lens as well as several other tissues. In this chapter, we will focus on the current knowledge regarding the molecular mechanisms by which αA- and αB-crystallins suppress apoptosis in both lens and non-lens tissues.