αB-crystallin (αBC) is a member of a small heat-shock protein (sHSP) superfamily and plays a predominant role in cellular protein homeostasis network by rescuing misfolded proteins from irreversible aggregation. αBC assembles into dynamic and polydisperse high molecular weight complexes containing 12 to 48 monomers; this variable stereochemistry of αBC has been linked to quaternary subunit exchange and its chaperone activity. The chaperone activity of αBC poses great potential as therapeutic agents for various neurodegenerative diseases. In this mini-review, we briefly outline the recent advancement in structural characterization of αBCs and its potential role to inhibit protein misfolding and aggregation in various human diseases. In particular, nuclear magnetic resonance (NMR) spectroscopy and its complimentary techniques have contributed much to elucidate highly-dynamic nature of αBCs, among which notable advancements are discussed in detail. We highlight the importance of resolving the structural details of various αBC oligomers, their quaternary dynamics, and structural heterogeneity.