Pseudoexfoliation syndrome (PEX) is a generalized extracellular matrix disorder with especially severe consequences in the anterior segment of the eye. Production and accumulation of an abnormal fibrillar protein (PEX material) and disturbed protection against oxidative stress in the anterior segment are considered the most important causes of the PEX-associated ocular alterations including PEX-glaucoma which is the most frequent type of secondary open-angle glaucoma. Why is PEX-material produced and why this production is clinically unilateral in many cases? The finding by Zenkel et al. (487) that aqueous humour level of clusterin, an extracellular chaperone with many different functions in many tissues is reduced in PEX may represent a step towards understanding this problem. Clusterin binds to unfolded proteins and prevents their aggregation, which is especially pronounced in case of slow aggregation process, like production of PEX-material. The authors measured aqueous humour clusterin level, in-vivo determined clusterin mRNA and protein expression on different human ocular tissues and investigated the effect of TGF-b1 on the expression in the non-pigmented ciliary cells. They found that compared to non-PEX controls, in the PEX eyes (but not in the clinically non-PEX fellow eye) aqueous humour clusterin level is reduced, clusterin mRNA expression is decreased in the anterior segment tissues, and clusterin mRNA and protein expression is downregulated by TGF-β 1 in the non-pigmented ciliary epithelial cells. Low aqueous clusterin level may provide decreased protection against protein misfolding, aggregation and accumulation, and therefore may play a role in the dysfunction of the trabecular meshwork. Since aqueous humour TGF-β 1 level is increased in PEX, it is especially interesting that TGF-β 1 exposition decreased clusterin expression. These findings add important information to the recent knowledge on the oxidative stress-induced complex alteration of the exfoliative eye.