Since Santiago Solari took charge of Real Madrid, Isco has been a starter in just two of the 16 matches and, with an injury crisis taking hold of the senior squad, it remains to be seen just what reason the Argentine coach can invent to not start the playmaker against Real Betis.
Only Mariano Diaz has started fewer matches under Solari than the former Malaga star, and that is hardly a role befitting of a player of Isco's salary and quality.
Injuries have taken hold at Valdebebas ahead of Sunday's clash against Quique Setien's side, with seven first-teamers all due to be unavailable.
Mariano, Gareth Bale, Marco Asensio, Toni Kroos, Marcos Llorente and Thibault Courtois will all miss out through injury, whilst Lucas Vazquez is suspended.
Vinicius Junior is suffering with a minor bout of flu after his heroics in the Copa del Rey victory over Leganes, so it is difficult to see just what footballing justification there could be for Isco not to start.
Yet, in truth, nobody dares predict such a starting role for Isco, such has been the discord between the pair and there could still be several reasons Solari could invent to avoid using Isco.
Four players in midfield
Without Kroos and Llorente, the midfield could be reinforced with four players positioned across the middle of the pitch. Casemiro and Federico Valverde could be positioned centrally with Dani Ceballos and Luka Modric acting as shuttle players just on either side of the aforementioned duo. This would leave Karim Benzema and Vinicius Junior as the two centre forwards, provided the Brazilian recovers from his ailment.
Start Brahim Diaz in a 4-3-3
The simpler solution would be for Solari to utilise his favoured 4-3-3 formation where the wingers are given freedom to cut into the central areas in attack. Isco doesn't fit naturally into this and the newly signed Brahim could fill a role on the right.
Play Marcelo in midfield
This may seem like the more outlandish option of the three choices, however given Marcelo's defensive frailties this term it may well make more sense than initially expected. Sergio Reguilon would be deployed at left-back with the Brazilian just ahead of him. Modric, Casemiro and Ceballos would then be expected to act as a rotating three in central positions with Marcelo given freedom to bomb forward without concern for what is going on behind him.