I'm working with new 4TB drives, and one of them just had a bad spot in a fairly awkward place.
The very first block of an ext4 partition was unreadable, and caused problems in booting, as well as anything else that wanted to scan partitions.
I overwrote the first 4K with zeroes, deleted the partition (with gdisk) and created a new unformatted partition to cover the area. Now that partition passes a read test, and I'm checking the other partitions.
The damaged partition has been inactive for a while, so I'm quite sure I have adequate backups. But now seems to be a time for me to learn -- lots of things have been going wrong, and I've been learning how to cope.