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Ptchd1 mediates opioid tolerance via cholesterol-dependent effects on μ-opioid receptor trafficking

Schematic of CePTR-25 and HsPTCHD1 proteins, and two graphs comparing MPE (%) vs. fentanyl concentration in wildtype (left) and ptr-25 mutant (right), showing a rightward shift in the mutants dose-response curve.

The Grill lab in collaboration with Dr. Kirill Martemyanov’s group (UF Scripps Biomedical Labs) has used unbiased forward genetics to identify the Patched family protein PTR-25/Ptchd1 as an ancient, conserved regulator of MOR trafficking that affects opioid tolerance from C. elegans through rodents. The team’s findings suggest Ptchd1 could be a potential molecular target for treating opioid addiction and dependence.