In contrast to the multitargeted covalent DUB inhibitorPR619, IsoLiPro, a lithium isobutyrate-l-prolinecoordination compound (Figure ), was reported as a small-molecule USP11 inhibitor that targetsUSP11 over USP25, and reduced tau and β-amyloid levels and improvescognitive function in Alzheimer’s disease models. Moreover, high-throughput virtual screeningbased on a USP11 homology model identified benzoxadiazole derivativesand pyrrolo-phenylamidine analogues (Figure ) as two promising scaffolds. However, paralogue selectivity was not investigated. Here, USP11 is linked to early-onset autosomal dominant Alzheimer disease.