The Ecuador international has shone for Brighton since his arrival from Villarreal in 2022.
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Estupinan now has less than two years to run on his current deal and talkSPORT says United have now opened talks with Brighton over his signing.
Also keen are AC Milan, with both fallen giants in need of a new left-back addition.
At United, there remains fitness concerns over Luke Shaw, while Milan have just sold Theo Hernandez to Al-Hilal.