The Biogen-Denali LRRK2 inhibitor trial failure, an RCT with 648 participants showing no slowing of Parkinson's progression, marks a pivotal setback. This randomized controlled study, larger than many prior neurodegenerative efforts, underscores how genetic discoveries from 2004 (Paisan-Ruiz et al., Neuron) do not easily translate to sporadic cases. A 2018 observational analysis suggested broad LRRK2 benefits, but lacked RCT rigor and had potential industry conflicts. The STAT coverage missed links to alpha-synuclein trial flops and the absence of biomarker stratification, which could explain null results in non-mutation carriers. Synthesizing these reveals systemic issues: overreliance on single targets without patient subgrouping risks repeated disappointments.