The LIM kinases (LIMK1/2) are key mediators in the multi-step signaling cascades that regulate actin cytoskeleton dynamics via cofilin phosphorylation. Dysregulation of these pathways and overexpression of LIMKs are implicated in disease development, including cancer, Fragile X syndrome, and glaucoma. Positioned downstream of the Rac/CDC42 signaling pathways, LIM kinases are attractive drug targets. Here, we targeted the LIMKs with PROTACs to disrupt both catalytic and non-catalytic mediated functions. Despite employing a dual LIMK1/2 inhibitor warhead and high structural conservation between the two human LIM kinases, we discovered isoform-specific LIMK2 degradation. We developed initial PROTACs into a highly potent and selective LIMK2 degrader. Cell-based assays and structural comparisons suggested that isoform specificity was likely driven by favorable orientation bias and/or lysine accessibility, along with enhanced ternary complex formation. Finally, we comprehensively characterized the PROTAC as a chemical probe, which induces isoform-specific degradation, which can be challenging to achieve with conventional reversible inhibitors.