The Prologue 21 utilizes a 50 pin SCSI hard drive that was originally between 512MB and 1GB to save settings and data. This drive is required to be accessed at boot from for the machine to function. Unfortunately, these drives are a somewhat common issue after decades of use. Sega Music Networks service had enough failures that, by at least 2003, they had a conversion kit ready to go for machines with failed hard drives to get them back in service. This included an interface board that would convert the SCSI connector to an IDE hard drive, where a 20GB IDE drive would be installed in place of the original 512MB or 1GB drive.
The original drives tend to have stuck platters that can sometimes be freed and work normally afterwards. Many issues past this will require replacement of the drive to fix, hopefully after a backup can be made.
As the interface is 50 pin SCSI, several modern drive replacements are available on the market. I have had great success with the Zuluscsi line of replacements.
If you do believe you need to replace the hard drive with another, or with a modern SD card replacement, be sure your Prologue has a SCSI terminator in the right SCSI port on the lower left of the rear I/O. I have seen several cases where certain hard drives will boot without the terminator present, but another drive or drive type in the same machine will require termination to function.
SEGA Prologue 21 