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Abstract β/γ-Crystallins are predominant structural proteins in vertebrate lens with unique properties of extremely high solubility, long-term stability and resistance to UV damage. Four conserved Trp residues in β/γ-crystallins account for UV absorbance and thereafter fluorescence quenching to avoid photodamage. Herein we found that βB2-crystallin Trp fluorescence was greatly enhanced by the introduction of an extra unquenched Trp fluorophore by cataract-associated mutations S31W and R145W. Both mutations impaired oligomerization, decreased stability and promote thermal aggregation, while S31W was more deleterious. S31W accelerated βB2-crystallin aggregation under UV damaging conditions, whereas R145W delayed. These observations suggested that the introduction of an extra Trp fluorophore had complicated effects on βB2-crystallin stability and aggregation against various stresses. Our findings highlight that the number of Trp fluorophores in β/γ-crystallin is evolutionarily optimized to exquisitely perform their structural roles in the lens. Graphical abstract Image 1 Highlights • S31W and R145W introduce an extra fluorophore in βB2-crystallin. • S31W and R145W destabilize βB2-crystallin and promote thermal aggregation. • S31W accelerates but R145W retards UV-induced aggregation of βB2-crystallin. • The number of Trp fluorophores in β/γ-crystallin is evolutionarily optimized. [ABSTRACT FROM AUTHOR]