As reviewed above, at the crux of thromboinflammation is the small family of GPCRs known as PARs, with PAR1 being the best known example and the one first targeted for this “war to the knife, and knife to the hilt.” One objective in the authors’ labs is to confirm that anti-inflammatory small-molecule modulators of PAR1 (the parmodulins) possess neuroprotective effects and acceptable drug-like properties (including safety and selectivity) that will justify their preclinical development to ultimately treat and potentially prevent ALS and other neurodegenerative diseases. This evidence concerns the gene MARK2 and amyotrophic lateral sclerosis.