Serum analyses identified four elevated soluble checkpoints in ALS versus both HCs and Mimics (sPD-1/sBTLA/sCTLA-4/sCD27, p < 0.05), with sCD28/TIM-3 showing higher in ALS than in Mimics, and sGITR/sCD137/sIDO/sCD80/sLAG3/sPD-L2 elevating in ALS compared to HCs. Here, HAVCR2 is linked to amyotrophic lateral sclerosis.