This analysis identified clusters of signaling systems that may be primarily affected by HD over time, highlighting not only proteasome-mediated protein catabolism (p=5.93 × 10−62) but also regulation of cell cycle (p=2.47 × 10−5: e.g., G1 and G2 transitions), senescence-associated secretory phenotypes (p=8.32 × 10−17), DNA repair (p=9.01 × 10−5), TGF-ß signaling (p=0.0019), and Rab-dependent vesicle trafficking (e.g., Rab1, Rac1, Gdi1, Chm) as primary targets of the combined gain of pathogenicity and loss of compensation in Drd1-MSNs. The gene discussed is GDI1; the disease is Huntington disease.